Postmenopausal women who have had hysterectomies can safely take estrogen-alone therapy without raising their breast-cancer risk, the latest analysis of data from a large but disconcerting U.S. study suggests.

The finding comes from the estrogen-alone arm of the Women's Health Initiative and contrasts dramatically with another part of the study, which reported three years ago that postmenopausal women given both estrogen and progestin showed a definite spike in breast-cancer risk.

Lead author Marcia Stefanick, a researcher at the Stanford University School of Medicine, hopes the latest findings will help clarify the issue for women unnerved by the seemingly contradictory results of hormone-replacement research.

"The good news is we confirmed the preliminary data that there was no increase in breast cancer in the study population overall, which was really different from the estrogen-plus-progestin trial," Dr. Stefanick said yesterday from Stanford, Calif.

"The issue for women who have had a hysterectomy with respect to the concern about breast cancer is very different from estrogen combined with progestin."

"If you have a uterus, you have a totally different issue to consider and that is: Going on hormones does increase your risk of breast cancer," she said, adding that a woman with an intact womb should not take just estrogen because of the risk of uterine cancer. (Estrogen, taken by itself, increases the risk of uterine cancer. So, women with an intact uterus usually take estrogen combined with progestin to counter the cancer-causing effect.)

The 15-year-long Women's Health Initiative has looked at the causes and prevention of conditions and diseases that affect women aged 50 and older -- among them, hormone-replacement therapy for hot flashes and other symptoms of menopause.

The estrogen-alone trial compared the effects of estrogen versus placebo in almost 11,000 women, aged 50 to 79, over seven years. The study was designed to conclude after eight years, but was halted 12 months early after increased rates of blood clots in the legs, and therefore, stroke were found among those taking estrogen.

Dr. Stefanick said the risk of stroke is highest for elderly women, as is the danger of fracturing a hip.

"When we talk about the menopause-aged women, most 50-year-old women are not at very high risk for stroke or hip fracture, so where they have the biggest concern is for breast cancer."

The study, published in today's edition of the Journal of the American Medical Association, found that the women taking estrogen had fewer breast-cancer tumours than those given a placebo and a lower incidence of hip fracture.

Women on estrogen were diagnosed with breast cancer at a rate of 28 per 10,000 per year, compared with 34 per 10,000 in the placebo group.

Dr. Stefanick said the difference between the groups is not statistically significant and could have occurred by chance.

However, the new analysis also found that participants taking estrogen had 50 per cent more abnormal mammograms requiring follow-up -- although abnormal mammograms do not necessarily signal cancer -- and 33 per cent more breast biopsies.

Women on estrogen tended to have larger tumours that were likely to have spread to lymph nodes, a finding that suggests estrogen might reduce the risk of smaller tumours but not larger ones, or that smaller tumours are not diagnosed early because of changes in breast tissue.

"The majority of tumours seen were small tumours, but when put altogether, women who got cancer on estrogen had larger tumours than women who got cancer who were on placebo," Dr. Stefanick said.

"Whether that's a cause and effect, we can't answer."

Commenting on the study, B.C. endocrinologist Jerilynn Prior said she is worried some people could misinterpret the study and believe estrogen taken alone could reduce breast-cancer risk because participants on the hormone had fewer tumours than those taking nothing.

"I really don't want women to think that estrogen would be a good thing for breast cancer," Dr. Prior said from Vancouver, noting that many studies have shown that the hormone can contribute to breast cancer in some women.

"I don't think it [the study] changes the message that hormones -- estrogen and progesterone or estrogen alone -- should be used other than for severe menopausal symptoms. . . . But I would also have a caveat on that. I think that the idea of using estrogen for menopausal symptoms carries the risk that when you stop it the symptoms will resume."

WHI director Elizabeth Nabel said more research is needed to explain the reduced number of breast cancers in women taking estrogen in the study.

"The findings still support current recommendations that hormone therapy should only be used to treat menopausal symptoms and should be used at the smallest effective dose for the shortest possible time," she said.

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